Contribution To Literature:

The COAPT trial showed that transcatheter mitral valve approximation using the MitraClip on a background of maximally tolerated GDMT was superior to GDMT alone in reducing HF hospitalization and mortality in symptomatic HF patients with grade 3-4+ MR.

Description:

The goal of the trial was to assess the safety and efficacy of transcatheter mitral leaflet approximation using MitraClip among symptomatic heart failure (HF) patients with secondary mitral regurgitation (MR).

Three-year outcomes: At 2 years, patients in the GDMT arm could cross over to the MitraClip arm if needed. As a result, total crossover was 18.6% (majority between 2 and 3 years). For the primary results, on ITT, there was still a profound benefit of MitraClip + GDMT over GDMT (annualized rates 35.5% vs. 68.8%, HR 0.49, 95% CI 0.37-0.63, p < 0.001). Benefit of MitraClip on mortality was preserved (42.8% vs. 55.5%, p = 0.001). Among the MitraClip patients, progressive HF requiring LVAD or heart transplant occurred in an additional 3.6% of patients (total 7.4%). Among the patients who crossed over, first HF hospitalization at 1 year was lower (13.8%), and the curves for the other clinical endpoints were more similar to the MitraClip arm than to the GDMT only arm, suggesting that benefit noted for the original MitraClip arm could be replicated in the control arm with MitraClip implantation (crossover).

Cost-effectiveness analysis: A patient-level economic analysis was performed combining data from COAPT and from a medical center for follow-up costs. The mean cost for the transcatheter mitral valve repair (TMVr) procedure was $35,755 (excluding physician fees), of which $30,628 was attributable to the cost of devices used in the procedure. After including ancillary costs and physician costs, the total cost of the index hospitalization was $48,198. Follow-up medical care costs were reduced by $11,690 per patient with TMVr vs. GDMT (95% CI -$20,714 to -$3,010; p = 0.018). However, when combined with the upfront cost of the initial TMVr admission, cumulative 2-year costs remained significantly higher with TMVr ($73,416 vs. $38,345; mean difference $35,072; 95% CI $26,370 to $44,085; p < 0.001). Under the base case scenario (benefits of MitraClip decreased between years 2 and 5, with no difference at 5 years), life expectancy was projected to be 6.12 years and 4.63 years for the MitraClip and GDMT groups, respectively. Based on these lifetime projections, the incremental cost-effectiveness ratio (ICER) for MitraClip vs. GDMT was $55,600/quality-adjusted life-year (QALY).

Health status changes: (n = 551; patients alive at 30 days) At least moderate improvement (≥10% increase in KCCQ-OS) was 58% for TMVr vs. 26% for GDMT. Early improvement in KCCQ-OS was inversely associated with the risk of death or HF hospitalization between 1 month and 2 years (p < 0.001). Every 10-point increase in KCCQ-OS from baseline to 1 month was associated with a 14% lower hazard of death or HF hospitalization during follow-up (HR 0.86, 95% CI 0.81-0.92, p < 0.001).

Interpretation:

The results of this landmark trial indicate that transcatheter mitral valve approximation using the MitraClip on a background of maximally tolerated GDMT was superior to GDMT alone in reducing HF hospitalization and mortality in symptomatic HF patients with grade 3-4+ MR. Improvements were also observed in LV dimensions and patient symptoms. Significant improvements were noted in QoL measurements starting at 1 month and sustained out to 24 months. The device had excellent safety.

All operators in this trial were experienced in the use of MitraClip. These results come on the heels of the recently published MITRA-FR trial, which did not show a benefit in this patient population. Possible reasons for differences include enrollment of patients with more severe MR (EROA >30 in COAPT vs. >20 in MITRA-FR) and less dilated ventricles (LVEDV 101 vs. 135, respectively). Procedural complications and success in reducing MR were also higher in the COAPT trial. These are truly landmark findings and will likely have a significant impact on the management of patients with secondary MR.

The cost-effectiveness analysis suggests higher costs with MitraClip compared with GDMT (mean difference approximately $35,000 over 2 years), with ICER analysis suggesting intermediate cost-effectiveness of MitraClip + GDMT over GDMT alone. This further underscores the need to carefully identify the patients most likely to benefit from MitraClip among patients with HF and MR.